CN-121622858-B - Application of Mashidu peptide in preparation of medicine for preventing or treating heart injury caused by doxorubicin

Abstract

The invention provides an application of a Mashi degree peptide in preparing a medicine for preventing or treating heart injury caused by doxorubicin. The invention belongs to the technical field of biological medicines, and particularly provides application of a Mashi degree peptide or a derivative thereof in preparation of a medicine for preventing or treating heart injury caused by doxorubicin. Through a plurality of experiments, the invention proves that the Marshi-degree peptide has better preventing and treating effects on cardiomyopathy and complications thereof caused by doxorubicin.

Inventors

• Cen xianfeng
• FANG WENXI
• FANG WENQIAN

Assignees

• 宁波市医疗中心李惠利医院(宁波大学附属李惠利医院)

Dates

Publication Date

20260508

Application Date

20260203

Claims (4)

1. 1. Application of a Marshi Du peptide in preparing medicine for preventing or treating myocardial injury caused by doxorubicin is provided.
2. 2. The use according to claim 1, wherein the medicament for preventing or treating myocardial damage caused by doxorubicin is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
3. 3. The use according to claim 1, wherein the medicament for preventing or treating myocardial damage caused by doxorubicin is in a pharmaceutically acceptable dosage form.
4. 4. The use according to claim 3, wherein the dosage form is at least one of an oral formulation, an injectable formulation, and an aerosol.

Description

Application of Mashidu peptide in preparation of medicine for preventing or treating heart injury caused by doxorubicin Technical Field The invention relates to the technical field of biological medicines, in particular to application of a Mashi degree peptide in preparation of a medicine for preventing or treating heart injury caused by doxorubicin. Background Doxorubicin (Doxorubicin, DOX) is used as an anthracycline broad-spectrum antitumor drug, and is widely used for treating various malignant tumors such as leukemia, breast cancer, lung cancer, lymphoma and the like, and has remarkable curative effect. However, its clinical application is severely limited by dose-dependent cardiotoxicity. Doxorubicin-induced cardiac injury is a complex pathological process involving a variety of mechanisms including, but not limited to, inhibition of nucleic acid and protein synthesis by intercalation of DNA, induction of mitochondrial dysfunction, induction of Reactive Oxygen Species (ROS) overproduction, induction of cardiac apoptosis and iron death, promotion of cardiac interstitial fibrosis, disruption of intracellular calcium ion homeostasis, and activation of sustained inflammatory responses. These pathological changes can ultimately lead to myocardial injury, decreased cardiac function, and may progress to heart failure, arrhythmias, or even dilated cardiomyopathy. At present, the control strategy for doxorubicin cardiotoxicity is very limited. Some antioxidants, such as vitamins E, N-acetylcysteine, resveratrol, etc., are often tried clinically in order to alleviate oxidative stress damage. However, the protective effect of these drugs is not ideal and the urgent clinical demands for high-efficiency, specific cardioprotective agents have not been met. Therefore, the research of new drugs and new targets which can effectively prevent or treat heart injury caused by doxorubicin has great clinical significance and application value. The Marshi-du peptide (Mazdutide) is a novel glucagon (GCG)/glucagon-like peptide-1 (GLP-1) dual receptor agonist. The known main application of the composition is as a hypoglycemic and weight-reducing medicament, and the composition has the potential of well improving blood sugar control, reducing weight and bringing multiple metabolism benefits (such as improving blood fat, reducing blood pressure and liver fat content and the like) in clinical researches. Based on the prior studies of GLP-1 receptor agonists, the drugs are proved to have potential beneficial effects on the cardiovascular system by increasing myocardial glucose uptake and oxidative utilization to optimize energy metabolism, reduce heart inflammatory response, inhibit myocardial fibrosis, reduce myocardial apoptosis and other pathways. However, the effect of the Mashi degree peptide on preventing or treating heart-specific damage induced by chemotherapeutic drugs such as doxorubicin has not been reported or suggested to date. Whether the Marshi degree peptide can be applied to the prevention and treatment of doxorubicin cardiomyopathy belongs to the unknown field completely. Disclosure of Invention The first aim of the invention is to provide an application of a Mashi degree peptide and a pharmaceutically acceptable derivative thereof in preparing medicines for preventing or treating heart injury caused by doxorubicin. In the invention, the Mashi degree peptide and the pharmaceutically acceptable derivatives thereof are in the form of pharmaceutically acceptable salts. In the invention, the Mashi degree peptide and the pharmaceutically acceptable derivatives thereof are in the form of pharmaceutically acceptable acid addition salts. The invention adopts the medicinal salt form (such as acid addition salt) to obviously improve the physicochemical properties of the Mashi degree peptide, such as stability, solubility and bioavailability, thereby ensuring the effectiveness of the Mashi degree peptide in the preparation and storage processes and facilitating the in vivo absorption to exert the heart protection effect. The limitation is based on the mature pharmaceutical salt chemistry technology, a specific implementation path of industrialization is defined, and the practicability of the invention is enhanced. Meanwhile, the protection range is reasonably expanded, various common stable forms of active ingredients are covered, the core inventive concept is not easy to avoid by simple salt type replacement, and the stability of patent rights is improved. In the invention, the cardiac injury caused by the doxorubicin is selected from one or more of myocardial injury, heart failure, arrhythmia and dilated cardiomyopathy. In the invention, the medicine for preventing or treating the heart injury caused by the doxorubicin is a medicine composition, and the medicine composition also comprises a pharmaceutically acceptable carrier. In the invention, the drug for preventing or treating the heart injury caused by the doxorubicin